Closing the Sex-Based Differences in Stroke Care: Insights from a Large Telestroke Network on Treatment and Postacute Management

Background: The evolution of ischemic stroke is different accordin'g to sex and is one of the main causes of death in women. Previous studies have shown that women are less likely to receive acute treatment, and stroke center type is an important predictor of door-to-needle times. We investigated whether women are attended in a similar way to men in the telestroke network with specialized stroke physicians. Methods: A prospective registry of ischemic strokes recorded in the centralized Andalusian telestroke network was analyzed, focusing on sex differences. Demographic data, clinical characteristics, neuroimaging data, treatment intervals, follow-up visits, and clinical outcomes were collected. Results: A total of 3009 suspected stroke patients were attended to in the telestroke network from 2019 to 2023, of which 42.74% were women. Women were older (p < 0.001) and less independent upon arrival (p = 0.006) than men. There was no difference in the treatment received or in the treatment time intervals between the groups. Importantly, there was no difference in modified Rankin scale scores at 3 months between sexes. At 3 months post-stroke follow-up, women had fewer imaging tests (p = 0.018) and fewer outpatient visits (p < 0.001) than men. Conclusions: No significant difference between men and women has been found in the acute treatment of stroke in a large telestroke network. However, the same is not true for the follow-up and management of patients after the acute phase. This fact supports that strict adherence to protocols and specialization of care lead to equal care that avoids sex differences in stroke treatment and functional outcomes.

patients after the acute phase.This fact supports that strict adherence to protocols and specialization of care lead to equal care that avoids sex differences in stroke treatment and functional outcomes.
Keywords: follow-up; sex; stroke; telestroke network Background Ischemic stroke is a global public health problem and constitutes one of the main causes of disability in adults.The clinical outcome of stroke differs between sexes, representing one of the main causes of death in women globally. 1Several studies have considered the female sex as an independent predictive factor of disability. 2 It has not yet been fully clarified whether this difference is because of sex dimorphism or to treatment and management discrepancies.Women have less frequent use of acute stroke medication-based guidelines and are also less likely to receive thrombolysis than men. 3 Moreover, women are older than men at stroke onset, a factor that could contribute to their comparatively worse outcome, despite adjustments for age differences. 1t is generally assumed that strokes of cardioembolic etiology because of atrial fibrillation are more frequent in women, whereas atherothrombotic strokes are more frequent in men. 1,4The differences in clinical outcomes after reperfusion therapies according to sex remain unclear; age and stroke severity at onset were found to be confounding factors in previous studies. 3,5nnovation in health care and new technologies offer a great opportunity to reduce health care disparities, particularly in stroke.Telestroke is defined as telemedicineenabled stroke consultation that allows patients to be treated in their local community hospital by an on-site physician with remote consultation by a specialist. 6he use of telestroke is now a class I recommendation by the American Heart Association. 7It is believed to have contributed to an overall increase in recombinant tissue plasminogen activator (rtPA) administration and reduced thrombolysis times, addressing geographic disparities in care.In this sense, it remains to be demonstrated whether these networks not only overcome the geographical problem but also inequalities in terms of sex or race.Previous studies have already suggested improving equity; however, findings remain inconclusive, 8 probably because of the study size or the diversity of the networks analyzed.
In this study, we aimed to explore stroke management and the clinical results according to the sex of patients with suspected strokes managed within a telestroke network.

Methods
A prospective registry of ischemic strokes recorded in the centralized Andalusian telestroke network was analyzed, focusing on sex differences.Andalusia is a region of Spain in southern Europe with an area of 87,597 km 2 and a population of 8,381,944 inhabitants.The telestroke network has six mechanical thrombectomy nodes.Each node is composed of one hub or comprehensive stroke center (CSC), one stroke unit (SU), and several telestroke spoke centers (THs).A vascular neurologist coordinates the program and provides consultations in the morning shift.A pool of vascular neurologists from the different stroke centers is on call for the remaining shift.In addition to recommending the most appropriate treatment for each patient, the neurologist decides whether the patient should be transferred to an SU or CSC based on the patient's individual needs and the resources available at each center at that time.
Picture archiving communication systems and medical records are centralized.
Owing to the convenience of having the entire population's medical records already centralized, network requirements are minimal, consisting mainly of a videoconferencing system (a smartphone with a 4G connection to each center and an on-call neurologist) to allow communication between professionals. 9emographic data, clinical characteristics, type of stroke, and risk factors (including age, diabetes, dyslipidemia, hypertension, smoking, alcohol intake, atrial fibrillation, and personal history of prior stroke/transient ischemic attack and heart disease) were collected for every patient.Neuroimaging evaluation of the current stroke was performed using computed tomography (CT), from which the ASPECTS score and the occluded vessel were determined.All CT are reviewed by the vascular neurologist and the local radiologist on call.
We collected data regarding treatment intervals.They were measured in each phase of the process (door-to-notification/activation time, door and notificationto-brain imaging time, door and notification-to-needle time, door-in-door-out time, door-origin and door-to-puncture femoral time, door-origin, and puncture-to-recanalization time).
Stroke severity was measured using the National Institute of Health Stroke Scale (NIHSS) performed by neurologists by videoconference.The follow-up of patients includes from acute hospitalization to 3 months postdischarge follow-up, adhering to the local protocol of the center where the patient was treated.The 3 months follow-ups were conducted either in person or via telephone, depending on the patient's situation and center protocol.This approach ensured comprehensive monitoring of patient progress and facilitated the collection of data on etiology, neuroimaging results, and the effectiveness of post-stroke interventions.Functional outcomes were evaluated with the modified Rankin Scale (mRS) at 90 days.

Statistical Analysis
Two-sample t tests or chi-square tests were used to compare the clinical characteristics between men and women (based on sex from birth).Candidate covariates included were age, sex, age-by-sex interaction, NIHSS score at admission, diabetes mellitus, hypertension, atrial fibrillation, heart failure, coronary artery disease, and prior stroke.
Differences between women and men in stroke care in the acute phase (treatment interval times), follow-up, and stroke outcomes (NIHSS score at discharge and mRS at 90 days) were explored using the chi-square test.
All statistical analyses were performed using STATA version 17 (STATA Corp., College Station, TX).All reported p values were based on two-tailed analyses; statistical significance was set at p < 0.05.

Results
A total of 3009 suspected stroke patients were attended to within tele-ictus network from 2019 to 2021, of whom 1286 (42.74%) were women.Women were older than men (69.96 -15.77 vs. 68.15-13.15 years, p < 0.001), and a total of 69.54% of the men and 63.85% of the women had been diagnosed with ischemic stroke during their telestroke consult (p = 0.002).Stroke mimics were diagnosed in a higher proportion in women than in men (22.70% vs. 16.34%,p = 0.001).The presence of diabetes mellitus, dyslipidemia, smoking, alcohol intake, previous stroke or TIA, and ischemic heart disease was significantly higher in men.In contrast, atrial fibrillation (31.55% vs. 26.07%,p = 0.038) was more frequent in women than in men.Regarding the ischemic stroke etiology, more cardioembolic strokes were found in women than in men (39.20% vs. 26.75%,p < 0.001).Complete baseline characteristics according to sex are shown in Table 1.Women also had more severe strokes, with higher NIHSS scores (median: 5, interquartile range [IQR] 1-10 vs. 4 IQR 1-9, p = 0.004).
Regarding radiological data, a higher percentage of men presented a favorable ASPECT (better than or equal to 6) than women in the initial CT (97.68 vs. 96.11,p = 0.013).The main locations of large vessel occlusion were M1 (37.63%) and M2 (23.48%) in women, while in men they were M1 (25.6%) and carotid internal artery (22.47%; p < 0.001).There was no significant difference in reperfusion treatment (24.25% in women vs. 24.91% in men, p = 0.699).There was also no difference when the treatment was analyzed separately, either in fibrinolytic (13.90% in women vs. 15.98% in men, p = 0.123) or in endovascular treatment (18.76% vs. 17.69%,p = 0.456), between groups.Regarding treatment intervals, there were no differences between the sexes (Table 2).
A total of 90.23% of men and 84.25% of women were admitted to one of the network hospitals (p < 0.001), but there was a difference in the service on admission.Men were admitted more frequently to a neurospecialized service (stroke unit, neurology ward, or neurointensive care) than women (52.34% vs. 60.40%,p = 0.001).Details are shown in Table 3.At follow-up, women had fewer neuroimaging tests than men (69.51% vs. 74.05%,p = 0.018).Among patients who had follow-up neuroimaging, CT was performed in a greater number of women (32.61% vs. 26.70%,p = 0.011) and magnetic resonance imaging in a greater number of men (65.22% vs. 71.02%,p = 0.015).

Discussion
Women have a higher burden of stroke mortality and disability than men. 10 However, it is not clear whether this is because of purely biological differences in the response to brain ischemia and ischemic risk or to a disparity in health care provision. 1Andalusia has been called the "Spanish Stroke Belt" on account of its high stroke mortality rate.A telestroke network was created to improve this statistic by reorganizing and improving stroke care in the region.In this way, inequalities between areas have been reduced since it has been achieved that almost the entire population is less than an hour away from a center where stroke treatment can be performed. 11egarding the acute phase and differences in health care provision between sexes, our data show that there are no important differences in the management of stroke in the acute phase with similar rates of treatments and interval times to treatment.Previous studies have shown that women are less likely to receive endovascular treatment or rtPA than men, even after adjusting for functional status before onset and the time from onset to the hospital door. 12,13Stroke center type was also an important hospital-level predictor of tPA utilization and times to treatment in previous studies, with differences in patients treated in a rural/ smaller hospital and those treated in metropolitan/ larger hospitals. 14,15Hospitals without specialized stroke care have longer delays, which is pronounced for women. 5One of the causes of treatment delays in women is the difficulty of diagnosis and presentation (stroke mimics are also more frequent in women in our study).However, this issue has been overcome with telestroke networks and specialized physicians.We also found longer times to reperfusion in men, probably related to proximal occlusions (internal carotid artery [ICA] and M1), which are more frequent in men and are usually of atheromatous origin that make the procedure more difficult.
Most studies have found that strokes are more severe in women than in men, although age may be a confounding factor.Although severity increases with age, previous studies have shown poor outcomes, even after adjusting for risk factor profile and age. 16he differences in the risk factor profile found in men and women seem to be one of the main points of interest.In general, most modifiable risk factors are found more frequently in men; however, women with  modifiable risk factors have a greater likelihood of developing a stroke. 17Moreover, atrial fibrillation and ischemic strokes are more frequent in women. 18,19hese profiles are also met in our study.
Although functional outcomes after stroke usually differ according to sex, our study demonstrates that with proper management in the acute phase following established protocols by vascular neurologists, these outcomes can be balanced.Thus, the mRS at 3 months in our study was similar between both sexes.However, although there are no differences in acute management, there are differences in patient follow-up.In this case, this follow-up is not guided by neurologists and is performed according to the center.Men are admitted to the neurology service more frequently than women.Reasons for this finding may be that women are older at the onset of stroke or their previous functional grade, which, although not statistically significant, the trend is toward a higher previous mRS in women.It is known that admission to stroke units and treatment by specialized physicians reduces mortality and dependency and is recommended by the main management guidelines.Even for hemorrhagic strokes with high dependency and subsidiary mortality, admission to the stroke unit is better than admission to intensive care. 20This different management may influence outcomes, and perhaps, the degree of dependence and mortality could be lower in women if they were treated the same as men.
Prior studies have shown that women are less likely than men to be investigated with standard diagnostic tests and that women admitted to hospitals with stroke are less likely to receive defect-free care. 11In our study, women had fewer neuroimaging tests after stroke.This fact causes women to have a higher percentage of misdiagnoses.This could be related to admissions to nonspecialized units, internal medicine in most cases, which also results in poor follow-up.Only onethird of patients have any follow-up visits in the months after acute treatment, and most of these patients are men.This may affect our results since we do not have complete data for all patients.However, this indicates the need for specialized physicians with adequate training who can guarantee a complete study of all patients to ensure adequate secondary prevention.
On the one hand, one of the limitations of the study is that it is observational, and some data might be missing.On the other hand, its great strength is the large number of patients included and its prospective nature.The large number and the fact that they reflect routine clinical practice make the results very reliable.
Much effort has been made to reduce sex-based differences in the acute management of stroke, but there is still a significant gap in subacute management.These differences could be overcome with a comprehensive strategy that addresses the existing issues, including further education of physicians and written protocols, remote support from tertiary care institutions, and implementation of future subacute clinical trials that test rural/urban strategies for stroke care.editing.J.M.: Conceptualization (lead); methodology, supervision, validation, review, and editing.

Table 2 .
Differences in Time Intervals between Women and Men

Table 3 .
Differences on Admission Unit between Women and Men